首乌方对左旋多巴诱导异动症大鼠的干预作用及其机制  

Effect and mechanism of Shouwu Fang on rats with levodopa-induced dyskinesia

作　　者：焦玥[1] 刘洋[1] 孙丹丹[1] 王丹巧[1] 梁嵘[2] 

机构地区：[1]中国中医科学院医学实验中心 北京市中医药防治重大疾病基础研究重点实验室,北京100700 [2]北京中医药大学基础医学院,北京100029

出　　处：《中国生化药物杂志》2015年第2期1-4,9,共5页Chinese Journal of Biochemical Pharmaceutics

基　　金：国家自然科学基金(81274121);中国中医科学院自主选题研究项目(ZZ2012010)

摘　　要：目的探讨首乌方对左旋多巴诱导的异动症(levodopa induced dyskinesia,LID)大鼠的干预作用及其机制。方法 32只雄性SPF级SD大鼠,随机分为4组:假手术组(sham operation,SO组)、异动症模型组(levodopa induced dyskinesia,LID组)、首乌方高剂量组(shouwufang-high dose,SWF-H组)、首乌方低剂量组(shouwufang-low dose,SWF-L组),每组8只。单侧双位点注射6-羟基多巴胺造成PD模型后,灌胃给予多巴丝肼(30 mg/kg)22 d诱发LID,首乌方剂量组同时灌胃(SWF-H含生药27 g/kg,SWF-L含生药18g/kg)。观察各组LID发病率并进行动物AIM评分;清醒自由活动状态下脑内纹状体微透析、水杨酸捕获羟自由基方法采样,高效液相-电化学检测动态观察病变靶器官细胞外液中羟自由基指标(2,3-DHBA、2,5-DHBA)的浓度变化;检测大鼠体内超氧化物歧化酶(SOD)及丙二醛(MDA)水平的变化。结果首乌方可明显降低大鼠LID的发病率及AIM评分,降低纹状体细胞外液2,3-DHBA及2,5-DHBA的浓度、并显著降低血清内MDA的水平。结论首乌方可以改善大鼠LID的行为学指标,有预防及干预LID的作用,其机制可能与减轻整体特别是病变靶器官的氧化应激损伤有关。Objective To investigate the effect of ShouwuFang （SWF） on levodopa-induced dyskinesia （LID） and its mechanism. Methods 32 SD rats were randomized into 4 group ： sham operation （SO） group, LID group, SWF low dose （SWF-L） group, and SWF high dose （ SWF-H ） group. Established the PD model by unilateral perfusion of 6-OHDA in two positions. The PD rats were administrated madopa （30 mg/kg）, madopa （30 mg/kg） ＋ SWF （27 g/kg）, or madopa （30 mg/kg） ＋ SWF （18 g/kg） for 22 days. Observed the incidence of LID and assessed the abnormal involuntary movement（AIM） scores in every group. Detected the dynamic change of hydroxyl free radicals indexes （concentration of 2,3-DHBA and 2,5- DHBA）, captured by salicylic acid in the extraeellular fluid of target tissue in free moving LID rats by brain microdialysis and HPLC-ED techniques; evaluated the changes of superoxide dismutase （SOD） and malondialdehyde （MDA） level in blood after microdialysis. Results SWF reduced the incidence of LID and AIM scores significantly, decreased the concentration of 2,3-DHBA and 2,5-DHBA in extraeellular fluids of striatum; meanwhile significantly decreased the MDA level in the serum. Conclusion SWF can improve the behavior and had the effect of prevention and protection on LID rats. Its mechanism is connected with reduction of oxidative stress damages in organism and especially in the target organs.

关 键 词：左旋多巴诱导异动症 氧化应激 首乌方 微透析 

分 类 号：R332[医药卫生—人体生理学]